Hydroxycholoroquine may protect against skin involvement in lupus

Lupus Foundation of America

Resource Content

What is the topic?

Many people with lupus develop skin rash early on in the course of their illness. This is especially true in people from minority populations, such as African-Americans and Hispanics. 

Hydroxychloroquine is a drug that treats malaria, but has been used successfully to treat people with lupus. These anti-malarial drugs may reduce disease flares and organ damage, as well as increase the lifespan for people with lupus. Anti-malarial drugs are not just used for skin involvement, but are widely prescribed for lupus patients due to their ability to reduce inflammation and delay the absorption of damaging ultraviolet light by the skin. 

What did the researchers hope to learn?

The researchers hoped to learn what factors have an impact on how much time it takes for a lupus patient to develop skin damage. 

Who was studied?

580 patients from a study called the “Lupus in Minorities, Nature verses Nurture (LUMIMA)” cohort were evaluated. Most of them were women with an average age of 37 who had lupus for about six years. Thirty-five percent of the patients were African-Americans, 29% were Caucasian, 20% were Texan-Hispanics, and 16% were of Puerto Rican-Hispanic background.        

How was the study conducted?

Patients from three different research centers participated in this five-year study. Each patient completed questionnaires and had genetic and laboratory testing performed. There were follow-up visits every six months during the first year of the study and yearly after that. Patients who developed skin rash before or at the time of enrollment in the study were excluded from analyses. The time it took for people to develop skin damage, if any, during the study was looked at. Skin damage was defined as the occurrence of at least one of the following problems for at least six months: thinning hair with scars on the scalp, extensive scarring on the skin, and open sores in the skin. If there was active inflammation in these areas, it was not counted since the idea was to only count damage that remained after the inflammation had been fully treated. 

Information about many other features of lupus, including symptoms and blood test results, were also collected from the patients when they entered the study. 

What did the researchers find?

39% of patients developed skin damage during the study. These patients included a higher proportion of women than those in the entire study and also included people from all of the different ethnicities represented in the study population. However, African-Americans experienced the highest frequency of skin damage. The frequencies of the different kinds of skin damage were: hair loss with scars (41%), extensive skin scarring (36%), and skin ulcers (13%). 

Geography and lifestyle did not seem to have any significant impact on how long it took for lupus patients to develop skin damage. People with discoid lupus developed damage more quickly than people with other kinds of rashes, as did people who had greater overall disease activity, damage to other parts of the body, or small blood clots under the fingernails. People with Raynaud’s (numbness and color changes of fingers or toes that get worse in the cold) took longer to develop skin damage. A number of other comparisons were made with blood test results and other lupus features that did not seem to have any impact on the results. 

When many questions are asked of one population of people, sometimes things can look like they are related to each other just due to randomness. This is a statistical problem that has to have mathematical corrections applied to it to improve the chances that the results are valid. In an initial uncorrected analysis, people who were taking any of the following drugs took longer to develop skin damage: hydroxychloroquine, aspirin, anti-inflammatory drugs (like ibuprofen or Aleve), and cholesterol-lowering drugs. After the statistics were adjusted to improve their validity, being Texas-Hispanic or Caucasian, or taking hydroxychloroquine, were now associated with a longer time to develop skin damage. 

84% of all of the patients had taken hydroxychloroquine. Among them, those who did not develop skin damage had been taking hydroxychloroquine more frequently than those who did (although the dose was the same). After five years, the risk of developing skin damage from lupus was reduced almost 5-fold in people taking hydroxychloroquine as compared to those who were not.        

What were the limitations of the study?

Information about important environmental factors, such as smoking, exposure to sunlight, use of sun blockers, and infections, was not looked at. These things could have affected the results in ways that are currently not clear. Also, even though some statistics were used to improve the validity of the data, all of these analyses were very dependent on something called a “model.” This means that the answer could still change if you ask the question differently or pair together different items in the statistical process.   

What do the results mean for you?

Hydroxychloroquine may help to delay the development of skin damage in some people with lupus. Since it is a very safe treatment if a person tolerates it well and continues to get their eyes checked at regular intervals, and since it is thought to have many benefits for people with lupus, this provides an additional reason to continue taking this drug when a person with lupus is feeling better.

Possible protective effects of hydroxychloroquine on delaying the occurrence of integument damage in lupus: LXXI, data from a multiethnic cohort.
Authors: Pons-Estel GJ, Alarcón GS, González LA, Zhang J, Vilá LM, Reveille JD, McGwin G Jr; Lumina Study Group. (2010). 
Arthritis Care & Research 62: 393-400.